Augmented cognitive training

Abstract

The present invention provides methods of treating cognitive deficits associated with mental retardation. The methods comprise combining cognitive training protocols and a general administration of phosphodiesterase 4 inhibitors.

1. A method comprising:
 a) administering a therapeutically effective dose of a phosphodiesterase 4 inhibitor to an animal in need of treatment of a cognitive deficit associated with Rubinstein-Taybi syndrome; and 
 b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with Rubinstein-Taybi syndrome; 
 
       wherein said phosphodiesterase 4 inhibitor is administered in conjunction with said training and enhances CREB pathway function during said training; 
       whereby said cognitive deficit is treated. 
     
     
       2. The method of  claim 1  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
       3. The method of  claim 1  wherein in step b), training comprises multiple training sessions. 
     
     
       4. The method of  claim 1  wherein said phosphodiesterase 4 inhibitor is administered before or during each training session. 
     
     
       5. The method of  claim 1  wherein said phosphodiesterase 4 inhibitor enhances CREB-dependent gene expression. 
     
     
       6. The method of  claim 1  wherein said animal is a mammal. 
     
     
       7. The method of  claim 6  wherein said mammal is a human. 
     
     
       8. The method of  claim 1 , wherein said phosphodiesterase 4 inhibitor is administered intraperitoneally or orally. 
     
     
       9. A method comprising:
 a) administering a therapeutically effective dose of a phosphodiesterase 4 inhibitor to an animal in need of treatment of a cognitive deficit associated with Rubinstein-Taybi syndrome; 
 b) providing a cognitive training protocol to said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with Rubinstein-Taybi syndrome; and 
 c) augmenting said cognitive training protocol by reducing the number of training sessions required to produce said improvement in performance relative to the improvement in performance obtained with cognitive training alone; 
 
       wherein said phosphodiesterase 4 inhibitor is administered in conjunction with said cognitive training and enhances CREB pathway function during said cognitive training. 
     
     
       10. A method comprising:
 a) administering a therapeutically effective dose of a phosphodiesterase 4 inhibitor to an animal in need of treatment of a cognitive deficit associated with Rubinstein-Taybi syndrome; 
 b) providing a cognitive training protocol to said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with Rubinstein-Taybi syndrome; and 
 c) augmenting said cognitive training protocol by reducing the number of training sessions required to produce said improvement in performance relative to the improvement in performance obtained with said cognitive training protocol alone; 
 
       wherein said phosphodiesterase 4 inhibitor is administered in conjunction with said cognitive training and enhances CREB pathway function during said cognitive training; and 
       wherein said phosphodiesterase inhibitor is administered in step a) for the purpose of augmenting said cognitive training protocol. 
     
     
       11. The method of  claim 10  wherein said phosphodiesterase 4 inhibitor is administered before or during each training session. 
     
     
       12. The method of  claim 10  wherein said phosphodiesterase 4 inhibitor enhances CREB-dependent gene expression. 
     
     
       13. The method of  claim 10  wherein said animal is a mammal. 
     
     
       14. The method of  claim 13  wherein said mammal is a human. 
     
     
       15. The method of  claim 9  wherein said phosphodiesterase 4 inhibitor is administered before or during each training session. 
     
     
       16. The method of  claim 9  wherein said phosphodiesterase 4 inhibitor enhances CREB-dependent gene expression. 
     
     
       17. The method of  claim 9  wherein said animal is a mammal. 
     
     
       18. The method of  claim 17  wherein said mammal is a human. 
     
     
       19. The method of  claim 9 , wherein said cognitive training protocol comprises spaced training sessions. 
     
     
       20. The method of  claim 10 , wherein said cognitive training protocol comprises spaced training sessions. 
     
     
       21. The method of  claim 1 , wherein said phosphodiesterase 4 inhibitor is administered intraperitoneally or orally. 
     
     
       22. The method of  claim 9 , wherein said phosphodiesterase 4 inhibitor is administered intraperitoneally or orally. 
     
     
       23. The method of  claim 10 , wherein said phosphodiesterase 4 inhibitor is administered intraperitoneally or orally.